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Immunologic and Antibody Responses in Patients Receiving GM-CSF, (Leukine, Sargramostim) as Adjuvant Therapy of Stage II (T4), III and IV Melanoma.

Phase 2
14 Years
Not Enrolling
Malignant Melanoma

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Trial Information

Immunologic and Antibody Responses in Patients Receiving GM-CSF, (Leukine, Sargramostim) as Adjuvant Therapy of Stage II (T4), III and IV Melanoma.

This is a pilot study to describe the immunological responses and clinical outcome
associated with administration of recombinant human Granulocyte Macrophage Colony
Stimulating Factor (GM-CSF) as surgical adjuvant therapy in patients with malignant melanoma
who are at high risk for recurrence (Stage II T4, III and IV). The immunological responses
include serum neopterin levels. In a sub-set of study participants, additional immunologic
testing will be done, including monocyte cytotoxicity to a melanoma cell line and phenotypic
and functional markers of dendritic and T cell activation in peripheral blood mononuclear
cells. The clinical end points of the study include safety, time to disease recurrence,
time to disseminated disease, and survival. Eligible patients are those with high-risk
melanoma who are clinically tumor free following surgery. Treatment will consist of GM-CSF
at 125 g/m2 once daily (maximum dose 250 g) for 14 days followed by 14 days of rest (28
day cycle) for 1 year. Clinical status will be monitored until death or until the patient
has been tumor free for five years, whichever event occurs first. Immunologic responses
will be determined pretreatment, at the end of the first 14 days of dosing (Day 15), after
the 14-day rest period (Day 29) and at the end of 14 days of dosing in cycles 6 (Day 155)
and 13 (Day 351). Clinical outcome will be determined according to patient risk group
(ultra-high risk Stage IIIC or IV versus high-risk Stage II T4, Stage IIIA and Stage IIIB).
The pilot study will also assess the association of the immunological responses with
clinical response and safety by patient risk group.

Inclusion Criteria:

- Eligible patients will be males or females with histologically proven melanoma.
Patients must have Stage II (T4), III, and IV malignant melanoma surgically resected
with no clinical evidence of disease by clinical, laboratory criteria or radiologic
examination as defined below.

- Individuals must be at least 14 years of age.

- Pregnant women are not eligible. Men and women will be required to use an effective
form of contraception.

- Patients requiring corticosteroid therapy or are receiving other forms of
immunotherapy are not eligible.

- Patients may have received immunotherapy for prior disease. They must have completed
therapy at least one month prior to study entry. Patients may not have received prior
chemotherapy or therapy with GM-CSF. Patients are permitted to receive adjuvant
radiation therapy but these patients will not be selected as part of the sub-set
undergoing studies of cellular immunologic responses since the radiation could alter
these responses. Based on the reults from one randomized, controlled clinical trial,
the LEUKINE product labeling contains the following contraindication: “Due to the
potential sensitivity of rapidly dividing hematopoietic progenitor cells, LEUKINE
should not be administered simultaneously with cytoxic chemotherapy or radiotherapy
or within 24 hours preceding or following chemotherapy or radiotherapy. In one
controlled study, patients with small cell lung cancer received LEUKINE and
concurrent thoracic radiotherapy and chemotherapy or the identical radiotherapy and
chemotherapy without LEUKINE. The patients randomized to LEUKINE had significantly
higher incidence of adverse events, including higher mortality and a higher incidence
of grade 4 infections and grade 3 or 4 thrombocytopenia.28” Other investigators have
reported that CM-CSF can be given safely with concurrent radiation therapy. These
contrasting results may be related to differences in the patient populations or
intensity and/or location of the site of radiotherapy in the body, among other
factors. GM-CSF has been administered safely in combination with radiation therapy
for treatment of head and neck cancers29,30 and has been used safely during regimens
that combine chemotherapy and radiation therapy.31

- Patients must undergo examination for evidence of residual disease, including
physical examination, CBC, chemistry panel, CT scan of the chest and abdomen (and
pelvis for lower extremity or lower trunk lesions), and single sequence with
gadolinium MRI or CT of the brain. A PET scan may be substituted for the CT of the
chest and abdomen (and pelvis). These tests must be negative for residual disease
before entry into the study.

- Administration of the protocol medication must be initiated within 90 days of the
definitive surgical excision rendering the patient NED.

Exclusion Criteria:

- Patients not meeting Inclusion Criteria described above

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

1 To describe the effect of GM-CSF adjuvant treatment of 125 ug/m2 once daily for 14 days followed by 14 days rest on immunological function as determined by serum neopterin levels (a measure of macrophage activation) and on serum levels of S100B.

Principal Investigator

Lynn E. Spitler, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Northern California Melanoma Center


United States: Institutional Review Board

Study ID:

GM-CSF 040906



Start Date:

September 2004

Completion Date:

July 2010

Related Keywords:

  • Malignant Melanoma
  • Malignant Melanoma
  • Adjuvant Therapy
  • Cytokine Therapy
  • Immunologic Testing
  • Melanoma



Northern California Melanoma CenterSan Francisco, California  94109